Bone pathology lecture 2

Babylon University Stage Fourth
College of Medicine Bone Pathology Lecture 2
Dr. Athraa Falah
Bone-Forming Tumors
Benign Bone-Forming Tumors
Osteoma
Osteoma is a benign slow-growing tumor of compact bone.
Grossly , these tumors appear as round to oval sessile tumors that project from the subperiosteal or endosteal surfaces of the cortex. They are usually solitary and are detected in middle-aged .
Microscopically, it is composed of dense, mature, predominantly lamellar bone.
-This lesion is benign and probably not a true neoplasm. Osteomas do not transform into osteosarcoma.
Malignant Bone-Forming Tumors
Osteosarcoma
Osteosarcoma is defined as a malignant mesenchymal tumor in which the cancerous cells produce bone matrix. It is the most common primary malignant tumor of bone, exclusive of myeloma and lymphoma, and accounts for approximately 20% of primary bone cancers.
Osteosarcoma occurs in all age groups but has a bimodal age distribution; 75% occur in patients younger than age 20. The smaller second peak occurs in the elderly, who frequently suffer from conditions known to be associated with the development of osteosarcoma—Paget disease, bone infarcts, and prior irradiation. Overall, men are more commonly affected than women (1.6:1).
The tumors usually arise in the metaphyseal region of the long bones of the extremities, and almost 60% occur about the knee. Any bone may be involved.


Pathogenesis.
-Osteosarcomas are associated with mutations in tumor suppressor genes: almost two thirds show mutations in the retinoblastoma(RB) gene and many also have mutations in the p53 gene.
-Osteosarcoma can develop in adults and children previously subjected to external, therapeutic radiation for another tumor such as lymphoma.
-When osteosarcoma arise in older patients, they almost always occur in the context of Paget disease or radiation exposure.
-Several pre-existing benign bone lesions are associated with an increased risk of developing osteosarcoma, including fibrous dysplasia, osteomyelitis, and bone marrow infarcts.
Morphology.
Grossly, osteosarcomas are bulky tumors that are gritty, gray-white, and often contain areas of hemorrhage and cystic degeneration . The tumors frequently destroy the surrounding cortices and produce soft tissue masses. They spread extensively in the medullary canal, infiltrating and replacing the marrow surrounding the pre-existing bone trabeculae. Infrequently, they penetrate the epiphyseal plate or enter the joint.
Microscopically, reveal:
-malignant cells with osteoblastic differentiation , the cells vary in size and shape and frequently have large hyperchromatic nuclei.
-Bizarre tumor giant cells are common, as are mitoses.
-The formation of bone(woven bone) by the tumor cells is characteristic of osteosarcoma .
-The neoplastic bone has a coarse, lacelike architecture but is also deposited in broad sheets or as primitive trabeculae.
-Cartilage or fibrous tissue, may be present in varying amounts. When malignant cartilage is abundant, the tumor is called chondroblastic osteosarcoma.
-About 50% to 60% of an individual tumor may demonstrate spontaneous necrosis.
Clinical Course.
Osteosarcomas typically present as painful and progressively enlarging masses. Sometimes a sudden fracture of the bone is the first symptom. As pain intensifies, the area becomes swollen and tender, and the adjacent joint becomes functionally limited.
These aggressive neoplasms spread through the bloodstream, and at the time of diagnosis, approximately 10% to 20% of patients have demonstrable pulmonary metastases. In those who die of the neoplasm, 90% have metastases to the lungs, bones, brain, and elsewhere.
Advances in treatment have substantially improved the prognosis of osteosarcoma. Long-term survival is 60% to 70%, compared with previous rates of 25%. Standard treatment now includes chemotherapy and limb-salvage therapy.
Cartilage-Forming Tumors
Cartilage tumors are characterized by the formation of hyaline or myxoid cartilage. As in most types of bone tumors, benign cartilage tumors are much more common than malignant ones.
Benign Cartilage-Forming tumors
Osteochondroma
-Osteochondroma, also known as an exostosis, is a benign cartilage-capped outgrowth of bone that is attached to the underlying skeleton by a bony stalk. It is a relatively common lesion and can be solitary or multiple.
-Multiple osteochondromas occur in multiple hereditary exostosis, which is an autosomal dominant hereditary disease.
-For unknown reasons, men are affected three times more often than women.
-Osteochondromas arise from the metaphysis near the growth plate of long tubular bones, especially about the knee.
Morphology
-Grossly, the smaller tumors are sessile, whereas the larger ones tend to be pedunculated. Characteristically, there is a cap of cartilage covered a bone tissue . -Microscopically, the cells resemble those of normal hyaline cartilage. The bulk of the lesion is made up of mature bone trabeculae located beneath the cartilaginous cap and containing normal bone marrow.
Enchondroma
Solitary chondroma (enchondroma) is a benign, intraosseous tumor composed of well-differentiated hyaline cartilage.
Although its neoplastic nature has been questioned, cytogenetic analyses show chromosomal abnormalities in some chondromas, suggesting that they are, in fact, neoplasms.
The diagnosis is made at any age, and many cases are entirely asymptomatic.
Malignant Cartilage-Forming tumor
Chondrosarcoma
Chondrosarcoma of the skeleton is about half as frequent as osteosarcoma and is the second most common malignant matrix-producing tumor of bone.
Patients with chondrosarcoma are usually age 40 or older. The pelvic bones, ribs , and shoulder girdle are the most common locations.
The tumor affects men twice as frequently as women and has no race predilection. Although a significant number of conventional chondrosarcomas arise in association with a pre-existing enchondroma, few develop within an osteochondroma, chondroblastoma, or fibrous dysplasia or in the setting of Paget disease.
Morphology.
Grossly,-The large bulky tumors are made up of nodules of gray-white, somewhat translucent glistening tissue.
-Spotty calcifications are typically present, and central necrosis may create cystic spaces. The malignant cartilage infiltrates the marrow space and surrounds pre-existing bony trabeculae.
Microscopically
-The tumors vary in degree of cellularity, cytologic atypia, and mitotic activity .
-Low-grade, or grade 1 lesions demonstrate mild hypercellularity, and the chondrocytes have plump vesicular nuclei with small nucleoli. Binucleate cells are sparse, and mitotic figures are difficult to find.
-By contrast, grade 3 chondrosarcomas are characterized by marked hypercellularity and extreme pleomorphism with bizarre tumor giant cells and mitoses.
-These tumors usually present as painful, progressively enlarging masses.
There is a direct correlation between the grade and the biologic behavior of the tumor. Fortunately, most conventional chondrosarcomas are indolent and fall into the range of grade 1 and grade 2.
The 5-year survival rates were 90%, 81%, and 43% for grades 1 through 3, respectively. None of the grade 1 tumors metastasized, whereas 70% of the grade 3 tumors disseminated.
Another prognostic feature is size. Tumors greater than 10 cm behave significantly more aggressively than smaller tumors. When chondrosarcomas metastasize, they spread preferentially to the lungs and skeleton.
The treatment of conventional chondrosarcoma is wide surgical excision.
Miscellaneous Tumors
Ewing Sarcoma
EWS is an uncommon malignant bone tumor composed of small, uniform, round cells. It represents only 5% of all bone tumors and is found in children and adolescents, with two thirds of cases occurring in patients younger than 20 years. Boys are affected more often than girls (2:1). EWS is very rare in blacks.

Pathogenesis:
-EWS is thought to arise from primitive marrow elements or immature mesenchymal cells.
-Virtually all (90%) of these tumors have a reciprocal translocation between chromosomes 11 and 22 [t(11;22)p(13;q12)], which results in the fusion of the amino terminus of the EWS1 gene to the carboxy terminus of the FLI-1 gene, which encodes a transcription factor.
-The resulting fusion protein acts as a constitutively active transcription factor that stimulates cell proliferation.
Morphology.
Grossly, Ewing sarcoma invade the cortex and periosteum, producing a soft tissue mass. The tumor is tan-white and frequently contains areas of hemorrhage and necrosis.
-Microscopically, it is composed of sheets of uniform small, round cells that are slightly larger than lymphocytes with few mitoses and little intervening stroma
The presence of Homer-Wright rosettes (where the tumor cells are arranged in a circle about a central fibrillary space) is indicative of neural differentiation.
Clinical features
Ewing sarcoma usually arise in the diaphyses of long tubular bones, especially the femur and the flat bones of the pelvis.
They present as painful enlarging masses, and the affected site is frequently tender, warm, and swollen. Some patients have systemic findings, including fever, elevated sedimentation rate, anemia, and leukocytosis, which mimic infection.
The treatment of Ewing sarcoma includes chemotherapy and surgical excision with or without radiation.
The advent of effective chemotherapy has dramatically improved the prognosis from a dismal 5% to 15% to a 75% 5-year survival; at least 50% are long-term cures.